1. Technical Field
The present invention relates to a method for producing a bicyclo[3.1.0]hexane derivative, which is a metabotropic glutamate receptor modulator useful as a pharmaceutical. Furthermore, the present invention relates to a novel intermediate compound produced in the above production process.
2. Related Art
An excitatory amino acid such as glutamic acid modulates various physiological processes such as long term potentiation (learning and memory), synaptic plasticity development, motor control, respiration, cardiovascular modulation, and perception in the central nervous system (CNS) of a mammal.
Glutamic acid acts via at least two different classes of receptor. One of the classes is an ionotropic glutamate (iGlu) receptor, which functions as a ligand-gated ion channel. The second class is a G protein- or second messenger-binding ‘metabotropic’ glutamate (mGluR) receptor. It appears that receptors of either class mediate normal synaptic transmission in accordance with an excitatory pathway. It also appears that they are involved in modification of synaptic binding from the development stage throughout the lifetime (ref. Schoepp, Bockaert, and Sladeczek, Trends in Pharmacol. Sci., 11, 508 (1990), and McDonald and Johnston, Brain Research Reviews, 15, 41 (1990)).
Various bicyclo[3.1.0]hexane derivative compounds are recognized as mGluR modulators. mGluR modulators are useful for the prevention or treatment of nervous system diseases such as schizophrenia, anxiety disorder, depression, bipolar disorder, epilepsy, drug dependence disease, cognitive disorder, Alzheimer's disease, Huntington's chorea, Parkinson's disease, dyskinesia accompanied by muscle rigidity, cerebral ischemic, encephalopathy, or head injury.
For example, as mGluR agonists, a 2-amino-6-fluorobicyclo[3.1.0]hexane derivative represented by Formula (IA) below and a pharmaceutically acceptable salt thereof have been disclosed (ref. U.S. Pat. No. 6,333,428).

In the formula, R11 and R12 are independently selected from the group consisting of    (1) hydrogen;    (2) a C1-10 alkyl group;    (3) a C3-8 cycloalkyl group; and    (4) a C3-8 cycloalkyl-C1-5 alkyl group. U.S. Pat. No. 6,333,428 above states that the compound of the invention may be a racemic modification or an enantiomer.
Other than U.S. Pat. No. 6,333,428 above, there are reports on methods for preparing mGluR modulators and intermediates therefor at a laboratory scale (ref. U.S. Pat. No. 6,825,375, and Nakazato et al., J. Med. Chem., 43, 4893 (2000)).
Furthermore, there are also reports on a production method that can cope with production of an mGluR modulator and an intermediate therefor on a larger scale (ref. WO05/47215, and Yasuda et al., J. Org. Chem., 70, 8027 (2005)).